Mosquito hemocyte biology


Mosquito immune cells (hemocytes) are influenced by mosquito physiology

At present, much of mosquito hemocyte biology has been unexplored, leaving many fundamental questions regarding hematopoiesis and immune cell function unknown. Our current knowledge of mosquito immune cells has been largely based on findings in other insect model systems, such as Drosophila, in which studies have primarily focused on immature larval stages. In addition, the hematophagous behavior of mosquitoes creates a unique biological system in an important disease vector to study immune cell dynamics and function.

Building on previous microarray experiments to analyze transcriptional changes in mosquito hemocytes, we performed the first comprehensive proteomic analysis of circulating mosquito hemocytes in response to feeding and infection status (Smith et al., 2016). Using a novel technique to isolate granulocytes from other mosquito blood cells, we enriched and subsequently performed mass spectrometry-based, relative quantitative proteomics analyses on mosquito phagocytic granulocytes (Smith et al., 2016).

Comparisons of the proteomic profiles to existing transcriptome data revealed new insights into hemocyte gene regulation, demonstrating that blood-feeding alone is able to initiate innate immune signaling in hemocytes independent of pathogen challenge (Smith et al., 2016). In addition, the results led to the identification of several candidate markers to distinguish hemocyte populations in future immunological studies. Together, these data further implicate the role of hemocytes as determinants of malaria parasite survival and suggest that these immune cells may be important components of an anticipatory response that may prime the mosquito immune system following blood-feeding. More importantly, these studies have also highlighted our limited understanding of the mechanisms that influence cellular immunity and immune cell dynamics in the mosquito host.

Current experiments are underway to further examine how mosquito physiology shapes hemocyte immune function and to develop new methods for their characterization. 


Hemocyte differentiation mediates immune responses that limit oocyst survival

Stemming from the initial characterization of LL3 in the mosquito innate immune response and establishing its role as a major antagonist of malaria parasite development (Smith et al., 2012), follow-up studies identified that LL3 was also expressed in hemocytes following ookinete invasion. Additional experiments established the integral role of both LL3 and the JAK/STAT pathway in promoting immune cell differentiation (Smith et al., 2015; Kwon et al., 2017).

These changes to the immune cell population are most markedly visualized through an increase in granulocyte populations. Continuing studies using laboratory colonies of Anopheles gambiae s.l. have demonstrated that the regulation of hemocyte differentiation is different amongst different mosquito strains (Kwon et al., 2017). This argues that genetic differences between mosquitoes may influence vector competence by displaying variability in the signals that limit oocyst survival.

Current work is exploring the signals that lead to hemocyte differentiation and the genes that promote the differentiation of individual hemocyte sub-types.